It is abundantly evident that cancer is a genetic disease. The integrity, replication, segregation and regulation of chromosomes play critical roles in the formation and progression of all types of cancer. In the past decades a large number of oncogenes and tumor suppressor genes have been identified, expression of which is critical in cancer formation and progression. Altered expression can result from epigenetic changes or alteration of gene or chromosome structure through a variety of mechanisms including DNA mutations, amplifications, rearrangements and loss. Understanding these and other basic mechanisms that affect chromosome metabolism is therefore critical to the study of cancer, and improved knowledge of fundamental mechanisms could improve cancer detection and treatments. Despite this, research on cancer is often focussed on specific types of cancer, specific chromosome aberrations, and specific molecular pathways, while research on fundamental genetic and epigenetic mechanisms frequently proceeds in basic science labs with little or no appreciation of the relevance for cancer cause and treatment. The Chromosome Metabolism and Cancer Training Program (CMCTP) seeks to bridge this gap by bringing together cancer researchers and basic scientists in one of the nation's leading Cancer Research institutions, the Fred Hutchinson Cancer Research Center (FHCRC). The purpose of the CMCTP is to excite young basic scientists who are researching universal mechanisms of chromosome structure and function and to encourage them to apply their results to cancer biology, while at the same time helping trainee cancer researchers learn more about innovative methods and ideas in fundamental science. For the last two project periods, the CMCTP has been funded for two predoctoral and five postdoctoral positions. For the last year, an ARRA Competitive Supplement has allowed us to increase to seven postdoctoral positions. We have had no trouble identifying qualified candidates. Trainees from the past 10 years have been successful in publishing the research supported by the CMCTP, and in building professional careers in cancer research. Former trainees in the CMCTP are now productive independent researchers in academia and biotechnology. Therefore, we are requesting continued support for this successful postdoctoral and graduate training program, and request funding of two predoctoral positions and six postdoctoral positions. PUBLIC HEALTH RELEVANCE: Training of new cancer researchers is important if past successes are to be continued. To this end, research laboratories take new students and post-doctoral scientists into their laboratories to provide them with training for careers in cancer research. This is an application for a research training grant to train pre-doctoral and post-doctoral scientists in the methods and interpretation of results from investigations into the structures of chromosomes and the expression of genes, in normal cells and in cancer cells.